The two prime requirements for a truly satisfactory enzyme model are a) that it possess a cavity that is complementary to the shape and size of the substrate molecule and b) that it possess functional groups appropriately arranged in space to allow interaction with the potential reactive site of the substrate molecule. Certain (1,1,1,1,)metacyclophanes called calixarenes (Gr. calix, basin; arene, indicating the presence of aromatic rings in the macrocyclic array) have the potential for satisfying both of these criteria, and it is with the synthesis, characterization, and chemistry of these compounds that the present study is concerned. A "one-step" method of synthesis of the calixarenes involves the condensation of p-substituted phenols with formaldehyde, the products of the condensation having been shown to be mixtures of cyclic oligomers (e.g. calix(4)arenes, calix(6)arenes, calix(8)arenes, etc.) separable into the several components. A "multi-step" synthesis of the calixarenes involves the sequential construction of a linear oligomer followed by its cyclization to the corresponding cyclic oligomer. By means of these methods it is possible, for example, to construct the calix(4)arene from p-phenylphenol, a calixarene of interest because of its deep cavity and because of the possibility of introducing functional groups into the 4' positions. The proposed research aims at improving and extending the methods of synthesis to yield calixarenes with various sizes and shapes of cavities, with various groups on the upper rim of the calix, with various degrees of conformational mobility, and with bridges of various sorts. After structural characterization they are to be studied for their chemical, physical, spectral, conformational, and catalytic properties with particular attention being given to their ability to catalyze ester and amide hydrolyses (chymotrypsin model), dihydroxyacetone phosphate condensations (aldolase model), farnesol phosphate cyclizations, dihydropyridine-carbondyl hydrogen transfer processes, and oxygen activation (catalase model) as well as their ability to act as selective protecting agents.